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A Novel Mutant of Human Papillomavirus Type 18 E6E7 Fusion Gene and its Transforming Activity

  • Zhou, Zhi-Xiang (College of Life Science and Bioengineering, Beijing University of Technology) ;
  • Zhao, Chen (College of Life Science and Bioengineering, Beijing University of Technology) ;
  • Li, Qian-Qian (College of Life Science and Bioengineering, Beijing University of Technology) ;
  • Zeng, Yi (College of Life Science and Bioengineering, Beijing University of Technology)
  • Published : 2014.09.15

Abstract

Background: Persistent human papillomavirus (HPV) infection, especially with high-risk types such as HPV16 and HPV18, has been identified as the primary cause of cervical cancer. E6 and E7 are the major onco-proteins of high-risk HPVs, which are consistently expressed in HPV infected tissues but absent in normal tissues and represent ideal therapeutic targets for immunotherapy of cervical cancer. Materials and Methods: In this study, the optimized fusion gene HPV18 E6E7 (HPV18 ofE6E7) was constructed according to genetic codon usage for human genes. At the same time, for safety future clinical application, a mutant of HPV18 ofE6E7 fusion gene was generated by site-directed mutagenesis at L52G for the E6 protein and C98G for the E7 protein. Results: HPV18-E6E7 mutant (HPV18 ofmE6E7) constructed in this work not only lost the transformation capability for NIH 3T3 cells and tumorigenicity in BALB/c nude mice, but also maintained very good stability and antigenicity. Conclusion: These results suggest that the mutant should undergo further study for application as a safe antigenspecific therapeutic vaccine for HPV18-associated tumors.

Keywords

Human papillomavirus 18;E6-E7;therapeutic vaccine;cervical cancer

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Cited by

  1. Immunotherapeutic Effects of Dendritic Cells Pulsed with a Coden-optimized HPV 16 E6 and E7 Fusion Gene in Vivo and in Vitro vol.16, pp.9, 2015, https://doi.org/10.7314/APJCP.2015.16.9.3843